Are protein folds atypical?

Hao Li, Chao Tang, Ned S. Wingreen

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Protein structures are a very special class among all possible structures. It has been suggested that a 'designability principle' plays a crucial role in nature's selection of protein sequences and structures. Here, we provide a theoretical base for such a selection principle, using a simple model of protein folding based on hydrophobic interactions. A structure is reduced to a string of Os and 1s, which represent the surface and core sites, respectively, as the backbone is traced. Each structure is therefore associated with one point in a high dimensional space. Sequences are represented by strings of their hydrophobicities and thus can be mapped into the same space. A sequence that lies closer to a particular structure in this space than to any other structures will have that structure as its ground state. Atypical structures, namely those far away from other structures in the high dimensional space, have more sequences that fold into them and are thermodynamically more stable. We argue that the most common folds of proteins are the most atypical in the space of possible structures.

Original languageEnglish (US)
Pages (from-to)4987-4990
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Apr 28 1998

All Science Journal Classification (ASJC) codes

  • General


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